tbuckley/cabot-search huggingface dataset:
The cost of inflammatory bowel disease in high-income settings: a Lancet Gastroenterology &amp; Hepatology Commission
Authors: Johan Burisch, Mirabella Zhao, Selwyn Odes, Peter De Cruz, Severine Vermeire, Charles N Bernstein, Gilaad G Kaplan, Dana Duricova, Dan Greenberg, Hans O Melberg, Mamoru Watanabe, Hyeong Sik Ahn, Laura Targownik, Valérie E H Pittet, Vito Annese, KT Park, Konstantinos H Katsanos, Marte L Høivik, Zeljko Krznaric, María Chaparro, Edward V Loftus, Peter L Lakatos, Javier P Gisbert, Willem Bemelman, Bjorn Moum, Richard B Gearry, Michael D Kappelman, Ailsa Hart, Marieke J Pierik, Jane M Andrews, Siew C Ng, Renata D'Inca, Pia Munkholm
Journal: The Lancet. Gastroenterology & hepatology (2023)
Confronting the evolution and expansion of anti-vaccine activism in the USA in the COVID-19 era
Authors: Richard M Carpiano, Timothy Callaghan, Renee DiResta, Noel T Brewer, Chelsea Clinton, Alison P Galvani, Rekha Lakshmanan, Wendy E Parmet, Saad B Omer, Alison M Buttenheim, Regina M Benjamin, Arthur Caplan, Jad A Elharake, Lisa C Flowers, Yvonne A Maldonado, Michelle M Mello, Douglas J Opel, Daniel A Salmon, Jason L Schwartz, Joshua M Sharfstein, Peter J Hotez
Journal: The Lancet (2023)
The effect of the Xpert HIV-1 Qual test on early infant diagnosis of HIV in Myanmar and Papua New Guinea: a pragmatic, cluster-randomised, stepped-wedge, open-label trial
Authors: Yasmin Mohamed, Hla Htay, Janet Gare, Andrew J B Vallely, Angela Kelly-Hanku, Win Lei Yee, Paul A Agius, Steven G Badman, Minh Duc Pham, Claire Nightingale, Xiang-Sheng Chen, Zure Kombati, Amelia Koata, Gloria Munnull, Selina Silim, Win Thein, Tin Maung Zaw, Latt Latt Kyaw, Mark Stoové, Suzanne M Crowe, David Anderson, Htay Htay Tin, Stanley Luchters
Journal: The Lancet HIV (2023)
Limited Relevance of the Very Low Risk Prostate Cancer Classification in the Modern Era: Results from a Large Institutional Active Surveillance Cohort
Authors: Kevin Shee, Janet E. Cowan, Ashwin Balakrishnan, Domenique Escobar, Kevin Chang, Samuel L. Washington, Hao G. Nguyen, Katsuto Shinohara, Matthew R. Cooperberg, Peter R. Carroll
Journal: European Urology (2023)
Re: NIHR Global Research Health Unit on Global Surgery. Routine Sterile Glove and Instrument Change at the Time of Abdominal Wound Closure to Prevent Surgical Site Infection (ChEETAh): A Pragmatic, Cluster-randomised Trial in Seven Low-income and Middle-income Countries. Lancet 2022;400:1767–76
Authors: Malte W. Vetterlein, Quoc-Dien Trinh, Thomas Seisen
Journal: European Urology (2023)
Reply to Kirti Singh, Swarnendu Mandal, Manoj Kumar Das, Prasant Nayak, and Sambit Tripathy’s Letter to the Editor re: Andreas Hiester, Yue Che, Achim Lusch, et al. Phase 2 Single-arm Trial of Primary Retroperitoneal Lymph Node Dissection in Patients with Seminomatous Testicular Germ Cell Tumors with Clinical Stage IIA/B (PRIMETEST). Eur Urol. In press. https://doi.org/10.1016/j.eururo.2022.10.021
Authors: Yue Che, Andreas Hiester, Peter Albers
Journal: European Urology (2023)
Impact of Morphology in the Genotype and Phenotype Correlation of Bilateral Macronodular Adrenocortical Disease (BMAD): A Series of Clinicopathologically Well-Characterized 35 Cases
Authors: Florian Violon, Lucas Bouys, Annabel Berthon, Bruno Ragazzon, Maxime Barat, Karine Perlemoine, Laurence Guignat, Benoit Terris, Jérôme Bertherat, Mathilde Sibony
Journal: Endocrine Pathology (2023)
Integrative Pan-Cancer Genomic and Transcriptomic Analyses of Refractory Metastatic Cancer
Authors: Yoann Pradat, Julien Viot, Andrey A. Yurchenko, Konstantin Gunbin, Luigi Cerbone, Marc Deloger, Guillaume Grisay, Loic Verlingue, Véronique Scott, Ismael Padioleau, Leonardo Panunzi, Stefan Michiels, Antoine Hollebecque, Gérôme Jules-Clément, Laura Mezquita, Antoine Lainé, Yohann Loriot, Benjamin Besse, Luc Friboulet, Fabrice André, Paul-Henry Cournède, Daniel Gautheret, Sergey I. Nikolaev
Journal: Cancer Discovery (2023)

Abstract Metastatic relapse after treatment is the leading cause of cancer mortality, and known resistance mechanisms are missing for most treatments administered to patients. To bridge this gap, we analyze a pan-cancer cohort (META-PRISM) of 1,031 refractory metastatic tumors profiled via whole-exome and transcriptome sequencing. META-PRISM tumors, particularly prostate, bladder, and pancreatic types, displayed the most transformed genomes compared with primary untreated tumors. Standard-of-care resistance biomarkers were identified only in lung and colon cancers—9.6% of META-PRISM tumors, indicating that too few resistance mechanisms have received clinical validation. In contrast, we verified the enrichment of multiple investigational and hypothetical resistance mechanisms in treated compared with nontreated patients, thereby confirming their putative role in treatment resistance. Additionally, we demonstrated that molecular markers improve 6-month survival prediction, particularly in patients with advanced breast cancer. Our analysis establishes the utility of the META-PRISM cohort for investigating resistance mechanisms and performing predictive analyses in cancer. Significance: This study highlights the paucity of standard-of-care markers that explain treatment resistance and the promise of investigational and hypothetical markers awaiting further validation. It also demonstrates the utility of molecular profiling in advanced-stage cancers, particularly breast cancer, to improve the survival prediction and assess eligibility to phase I clinical trials. This article is highlighted in the In This Issue feature, p. 1027
Meet the First Authors
Authors: Lingli Wang, Yuxi Sun, Mengqiu Ma, Ying Zhang
Journal: Circulation Research (2023)

before joining the Rabinovitch lab, where she has been a Research Scientist for the past 14 years.In addition to managing the lab and genotyping and phenotyping the extensive transgenic mouse colonies, Dr. Wang has pursued her own research project, investigating how a genetic mutation subverts smooth muscle cell function in pulmonary arterial hypertension.Lingli encourages lab members by reassuring them that, "continuous effort will lead to success".Outside the lab, she enjoys cooking for her family and jogging. Deep Phenotyping Heart-Specific Tregs (p 565)
Wearable Devices in Cardiovascular Medicine
Authors: Andrew Hughes, Md Mobashir Hasan Shandhi, Hiral Master, Jessilyn Dunn, Evan Brittain
Journal: Circulation Research (2023)

Wearable devices, such as smartwatches and activity trackers, are commonly used by patients in their everyday lives to manage their health and well-being. These devices collect and analyze long-term continuous data on measures of behavioral or physiologic function, which may provide clinicians with a more comprehensive view of a patients' health compared with the traditional sporadic measures captured by office visits and hospitalizations. Wearable devices have a wide range of potential clinical applications ranging from arrhythmia screening of high-risk individuals to remote management of chronic conditions such as heart failure or peripheral artery disease. As the use of wearable devices continues to grow, we must adopt a multifaceted approach with collaboration among all key stakeholders to effectively and safely integrate these technologies into routine clinical practice. In this Review, we summarize the features of wearable devices and associated machine learning techniques. We describe key research studies that illustrate the role of wearable devices in the screening and management of cardiovascular conditions and identify directions for future research. Last, we highlight the challenges that are currently hindering the widespread use of wearable devices in cardiovascular medicine and provide short- and long-term solutions to promote increased use of wearable devices in clinical care.
Rapid and sustained improvements in Generalized Pustular Psoriasis Physician Global Assessment scores with spesolimab for treatment of generalized pustular psoriasis flares in the randomized, placebo-controlled Effisayil 1 study
Authors: Boni E. Elewski, Mark G. Lebwohl, Milan J. Anadkat, Jonathan Barker, Kamran Ghoreschi, Shinichi Imafuku, Ulrich Mrowietz, Ling Li, Manuel Quaresma, Christian Thoma, Hervé Bachelez
Journal: Journal of the American Academy of Dermatology (2023)
Partisans’ receptivity to persuasive messaging is undiminished by countervailing party leader cues
Authors: Ben M. Tappin, Adam J. Berinsky, David G. Rand
Journal: Nature Human Behaviour (2023)

It is widely assumed that party identification and loyalty can distort partisans' information processing, diminishing their receptivity to counter-partisan arguments and evidence. Here we empirically evaluate this assumption. We test whether American partisans' receptivity to arguments and evidence is diminished by countervailing cues from in-party leaders (Donald Trump or Joe Biden), using a survey experiment with 24 contemporary policy issues and 48 persuasive messages containing arguments and evidence (N = 4,531; 22,499 observations). We find that, while in-party leader cues influenced partisans' attitudes, often more strongly than the persuasive messages, there was no evidence that the cues meaningfully diminished partisans' receptivity to the messages—despite them directly contradicting the messages. Rather, persuasive messages and countervailing leader cues were integrated as independent pieces of information. These results generalized across policy issues, demographic subgroups and cue environments, and challenge existing assumptions about the extent to which party identification and loyalty distort partisans' information processing. In a study examining 24 US policy issues and 48 persuasive information treatments, the authors find no evidence that US partisans' receptivity to persuasive information is diminished by countervailing cues from favoured party leaders.
Transcription of MERVL retrotransposons is required for preimplantation embryo development
Authors: Akihiko Sakashita, Tomohiro Kitano, Hirotsugu Ishizu, Youjia Guo, Harumi Masuda, Masaru Ariura, Kensaku Murano, Haruhiko Siomi
Journal: Nature Genetics (2023)

Zygotic genome activation (ZGA) is a critical postfertilization step that promotes totipotency and allows different cell fates to emerge in the developing embryo. MERVL (murine endogenous retrovirus-L) is transiently upregulated at the two-cell stage during ZGA. Although MERVL expression is widely used as a marker of totipotency, the role of this retrotransposon in mouse embryogenesis remains elusive. Here, we show that full-length MERVL transcripts, but not encoded retroviral proteins, are essential for accurate regulation of the host transcriptome and chromatin state during preimplantation development. Both knockdown and CRISPRi-based repression of MERVL result in embryonic lethality due to defects in differentiation and genomic stability. Furthermore, transcriptome and epigenome analysis revealed that loss of MERVL transcripts led to retention of an accessible chromatin state at, and aberrant expression of, a subset of two-cell-specific genes. Taken together, our results suggest a model in which an endogenous retrovirus plays a key role in regulating host cell fate potential.
Rare CNVs and phenome-wide profiling highlight brain structural divergence and phenotypical convergence
Authors: Jakub Kopal, Kuldeep Kumar, Karin Saltoun, Claudia Modenato, Clara A. Moreau, Sandra Martin-Brevet, Guillaume Huguet, Martineau Jean-Louis, Charles-Olivier Martin, Zohra Saci, Nadine Younis, Petra Tamer, Elise Douard, Anne M. Maillard, Borja Rodriguez-Herreros, Aurèlie Pain, Sonia Richetin, Leila Kushan, Ana I. Silva, Marianne B. M. van den Bree, David E. J. Linden, Michael J. Owen, Jeremy Hall, Sarah Lippé, Bogdan Draganski, Ida E. Sønderby, Ole A. Andreassen, David C. Glahn, Paul M. Thompson, Carrie E. Bearden, Sébastien Jacquemont, Danilo Bzdok
Journal: Nature Human Behaviour (2023)
Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus
Authors: Iain Mathieson, Felix R. Day, Nicola Barban, Felix C. Tropf, David M. Brazel, Diana van Heemst, Ahmad Vaez, Natalie van Zuydam, Bárbara D. Bitarello, Eugene J. Gardner, Evelina T. Akimova, Ajuna Azad, Sven Bergmann, Lawrence F. Bielak, Dorret I. Boomsma, Kristina Bosak, Marco Brumat, Julie E. Buring, David Cesarini, Daniel I. Chasman, Jorge E. Chavarro, Massimiliano Cocca, Maria Pina Concas, George Davey Smith, Gail Davies, Ian J. Deary, Tõnu Esko, Jessica D. Faul, Oscar Franco, Andrea Ganna, Audrey J. Gaskins, Andrea Gelemanovic, Eco J. C. de Geus, Christian Gieger, Giorgia Girotto, Bamini Gopinath, Hans Jörgen Grabe, Erica P. Gunderson, Caroline Hayward, Chunyan He, Diana van Heemst, W. David Hill, Eva R. Hoffmann, Georg Homuth, Jouke Jan Hottenga, Hongyang Huang, Elina Hyppӧnen, M. Arfan Ikram, Rick Jansen, Magnus Johannesson, Zoha Kamali, Sharon L. R. Kardia, Maryam Kavousi, Annette Kifley, Tuomo Kiiskinen, Peter Kraft, Brigitte Kühnel, Claudia Langenberg, Gerald Liew, Peter J. van der Most, Penelope A. Lind, Jian’an Luan, Reedik Mägi, Patrik K. E. Magnusson, Anubha Mahajan, Nicholas G. Martin, Hamdi Mbarek, Mark I. McCarthy, George McMahon, Sarah E. Medland, Thomas Meitinger, Andres Metspalu, Evelin Mihailov, Lili Milani, Stacey A. Missmer, Paul Mitchell, Stine Møllegaard, Dennis O. Mook-Kanamori, Anna Morgan, Peter J. van der Most, Renée de Mutsert, Matthias Nauck, Ilja M. Nolte, Raymond Noordam, Brenda W. J. H. Penninx, Annette Peters, Patricia A. Peyser, Ozren Polašek, Chris Power, Ajka Pribisalic, Paul Redmond, Janet W. Rich-Edwards, Paul M. Ridker, Cornelius A. Rietveld, Susan M. Ring, Lynda M. Rose, Rico Rueedi, Vallari Shukla, Jennifer A. Smith, Stasa Stankovic, Kári Stefánsson, Doris Stöckl, Konstantin Strauch, Morris A. Swertz, Alexander Teumer, Gudmar Thorleifsson, Unnur Thorsteinsdottir, A. Roy Thurik, Nicholas J. Timpson, Constance Turman, André G. Uitterlinden, Melanie Waldenberger, Nicholas J. Wareham, David R. Weir, Gonneke Willemsen, Jing Hau Zhao, Wei Zhao, Yajie Zhao, Harold Snieder, Marcel den Hoed, Ken K. Ong, Melinda C. Mills, John R. B. Perry
Journal: Nature Human Behaviour (2023)
Archway Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration 2-Year Results
Authors: Carl Regillo, Brian Berger, Logan Brooks, W. Lloyd Clark, Robert Mittra, Charles C. Wykoff, Natalia F. Callaway, Stephanie DeGraaf, Han Ting Ding, Anne E. Fung, Shamika Gune, Sophie Le Pogam, Robert Smith, Jeffrey R. Willis, Giulio Barteselli
Journal: Ophthalmology (2023)
Codon-specific KRAS mutations predict survival benefit of trifluridine/tipiracil in metastatic colorectal cancer
Authors: Joris van de Haar, Xuhui Ma, Salo N. Ooft, Pim W. van der Helm, Louisa R. Hoes, Sara Mainardi, David J. Pinato, Kristi Sun, Lisa Salvatore, Giampaolo Tortora, Ina Valeria Zurlo, Silvana Leo, Riccardo Giampieri, Rossana Berardi, Fabio Gelsomino, Valeria Merz, Federica Mazzuca, Lorenzo Antonuzzo, Gerardo Rosati, Chara Stavraka, Paul Ross, Maria Grazia Rodriquenz, Michele Pavarana, Carlo Messina, Timothy Iveson, Federica Zoratto, Anne Thomas, Elisabetta Fenocchio, Margherita Ratti, Ilaria Depetris, Massimiliano Cergnul, Cristina Morelli, Michela Libertini, Alessandro Parisi, Michele De Tursi, Nicoletta Zanaletti, Ornella Garrone, Janet Graham, Raffaella Longarini, Stefania Maria Gobba, Angelica Petrillo, Emiliano Tamburini, Nicla La Verde, Fausto Petrelli, Vincenzo Ricci, Lodewyk F. A. Wessels, Michele Ghidini, Alessio Cortellini, Emile E. Voest, Nicola Valeri
Journal: Nature Medicine (2023)

Abstract Genomics has greatly improved how patients with cancer are being treated; however, clinical-grade genomic biomarkers for chemotherapies are currently lacking. Using whole-genome analysis of 37 patients with metastatic colorectal cancer (mCRC) treated with the chemotherapy trifluridine/tipiracil (FTD/TPI), we identified KRAS codon G12 ( KRAS G12 ) mutations as a potential biomarker of resistance. Next, we collected real-world data of 960 patients with mCRC receiving FTD/TPI and validated that KRAS G12 mutations were significantly associated with poor survival, also in analyses restricted to the RAS / RAF mutant subgroup. We next analyzed the data of the global, double-blind, placebo-controlled, phase 3 RECOURSE trial ( n = 800 patients) and found that KRAS G12 mutations ( n = 279) were predictive biomarkers for reduced overall survival (OS) benefit of FTD/TPI versus placebo (unadjusted interaction P = 0.0031, adjusted interaction P = 0.015). For patients with KRAS G12 mutations in the RECOURSE trial, OS was not prolonged with FTD/TPI versus placebo ( n = 279; hazard ratio (HR) = 0.97; 95% confidence interval (CI) = 0.73–1.20; P = 0.85). In contrast, patients with KRAS G13 mutant tumors showed significantly improved OS with FTD/TPI versus placebo ( n = 60; HR = 0.29; 95% CI = 0.15–0.55; P &lt; 0.001). In isogenic cell lines and patient-derived organoids, KRAS G12 mutations were associated with increased resistance to FTD-based genotoxicity. In conclusion, these data show that KRAS G12 mutations are biomarkers for reduced OS benefit of FTD/TPI treatment, with potential implications for approximately 28% of patients with mCRC under consideration for treatment with FTD/TPI. Furthermore, our data suggest that genomics-based precision medicine may be possible for a subset of chemotherapies.
Drug repurposing in autosomal dominant polycystic kidney disease
Authors: Julie Xia Zhou, Vicente E. Torres
Journal: Kidney International (2023)

Autosomal dominant polycystic kidney disease is characterized by progressive kidney cyst formation that leads to kidney failure. Tolvaptan, a vasopressin 2 receptor antagonist, is the only drug approved to treat patients with autosomal dominant polycystic kidney disease who have rapid disease progression. The use of tolvaptan is limited by reduced tolerability from aquaretic effects and potential hepatotoxicity. Thus, the search for more effective drugs to slow down the progression of autosomal dominant polycystic kidney disease is urgent and challenging. Drug repurposing is a strategy for identifying new clinical indications for approved or investigational medications. Drug repurposing is increasingly becoming an attractive proposition because of its cost-efficiency and time-efficiency and known pharmacokinetic and safety profiles. In this review, we focus on the repurposing approaches to identify suitable drug candidates to treat autosomal dominant polycystic kidney disease and prioritization and implementation of candidates with high probability of success. Identification of drug candidates through understanding of disease pathogenesis and signaling pathways is highlighted.
A deep-learning algorithm to classify skin lesions from mpox virus infection
Authors: Alexander H. Thieme, Yuanning Zheng, Gautam Machiraju, Chris Sadee, Mirja Mittermaier, Maximilian Gertler, Jorge L. Salinas, Krithika Srinivasan, Prashnna Gyawali, Francisco Carrillo-Perez, Angelo Capodici, Maximilian Uhlig, Daniel Habenicht, Anastassia Löser, Maja Kohler, Maximilian Schuessler, David Kaul, Johannes Gollrad, Jackie Ma, Christoph Lippert, Kendall Billick, Isaac Bogoch, Tina Hernandez-Boussard, Pascal Geldsetzer, Olivier Gevaert
Journal: Nature Medicine (2023)

Abstract Undetected infection and delayed isolation of infected individuals are key factors driving the monkeypox virus (now termed mpox virus or MPXV) outbreak. To enable earlier detection of MPXV infection, we developed an image-based deep convolutional neural network (named MPXV-CNN) for the identification of the characteristic skin lesions caused by MPXV. We assembled a dataset of 139,198 skin lesion images, split into training/validation and testing cohorts, comprising non-MPXV images ( n = 138,522) from eight dermatological repositories and MPXV images ( n = 676) from the scientific literature, news articles, social media and a prospective cohort of the Stanford University Medical Center ( n = 63 images from 12 patients, all male). In the validation and testing cohorts, the sensitivity of the MPXV-CNN was 0.83 and 0.91, the specificity was 0.965 and 0.898 and the area under the curve was 0.967 and 0.966, respectively. In the prospective cohort, the sensitivity was 0.89. The classification performance of the MPXV-CNN was robust across various skin tones and body regions. To facilitate the usage of the algorithm, we developed a web-based app by which the MPXV-CNN can be accessed for patient guidance. The capability of the MPXV-CNN for identifying MPXV lesions has the potential to aid in MPXV outbreak mitigation.
Lysosomal control of senescence and inflammation through cholesterol partitioning
Authors: Kyeonghwan Roh, Jeonghwan Noh, Yeonju Kim, Yeji Jang, Jaejin Kim, Haebeen Choi, Yeonghyeon Lee, Moongi Ji, Donghyun Kang, Mi-Sung Kim, Man-Jeong Paik, Jongkyeong Chung, Jin-Hong Kim, Chanhee Kang
Journal: Nature Metabolism (2023)
Evidence of a predictive coding hierarchy in the human brain listening to speech
Authors: Charlotte Caucheteux, Alexandre Gramfort, Jean-Rémi King
Journal: Nature Human Behaviour (2023)

Abstract Considerable progress has recently been made in natural language processing: deep learning algorithms are increasingly able to generate, summarize, translate and classify texts. Yet, these language models still fail to match the language abilities of humans. Predictive coding theory offers a tentative explanation to this discrepancy: while language models are optimized to predict nearby words, the human brain would continuously predict a hierarchy of representations that spans multiple timescales. To test this hypothesis, we analysed the functional magnetic resonance imaging brain signals of 304 participants listening to short stories. First, we confirmed that the activations of modern language models linearly map onto the brain responses to speech. Second, we showed that enhancing these algorithms with predictions that span multiple timescales improves this brain mapping. Finally, we showed that these predictions are organized hierarchically: frontoparietal cortices predict higher-level, longer-range and more contextual representations than temporal cortices. Overall, these results strengthen the role of hierarchical predictive coding in language processing and illustrate how the synergy between neuroscience and artificial intelligence can unravel the computational bases of human cognition.
Molecular and cellular mechanisms of the first social relationship: A conserved role of 5-HT from mice to monkeys, upstream of oxytocin
Authors: Yan Liu, Liang Shan, Tiane Liu, Juan Li, Yongchang Chen, Changhong Sun, Chaojuan Yang, Xiling Bian, Yuyu Niu, Chen Zhang, Jianzhong Xi, Yi Rao
Journal: Neuron (2023)